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Dissertation
Inhibition of macrophage-induced, antigen-specific T lymphocyte proliferation by poly I:C
Doctor of Philosophy (Ph.D.), Medical College of Pennsylvania
1992
DOI:
https://doi.org/10.17918/00007747
Abstract
Peritoneal macrophages (M[phi]) from mice treated with poly I:C prior to pulsing with antigen, fail to induce antigen-specific T cell proliferation. The current study investigated the mechanism of this inhibition. The inhibition of T cell proliferation was shown to be antigen-specific and was not limited to one particular H-2 type or to one antigen. This inhibition is not mediated by the generation of prostaglandins, other soluble suppressor factors, or suppressor/cytotoxic M[phi]. These results suggested that poly I:C treated M[phi] failed to produce activation signals required for stimulation of T cell proliferation. Poly I:C treated, KLH-pulsed M[phi] were activated as demonstrated by a decrease in the specific activity of ectoenzymes, decreased expression of the M[phi]-specific cell surface marker F4/80 and increased cytoplasmic vacuolarization. However, the ability of poly I:C treated, KLH-pulsed M[phi] to spread on plastic was delayed compared to saline treated, KLH-pulsed controls. The addition of IL-1, IL-2, IL-6 or combinations of IL-1 and IL-6 to cultures could not reverse the inhibition of antigen-specific T cell proliferation. Further, the expression of class II major histocompatibility (Ia) molecules by poly I:C treated, KLH-pulsed was similar to that expressed on saline-treated, KLH-pulsed M[phi]. The ability of poly I:C treated M[phi] to induce the proliferation of an antigen-specific T cell hybridoma, but not primary, resting T cells suggested that poly I:C did not affect the processing of antigen, but rather may be modulating a signal necessary for the induction of resting T cell proliferation. The proliferation of KLH-immune T cells cultured with poly I:C treated M[phi] could be restored by the addition of allogeneic M[phi] (allo-M[phi]). This increased proliferation was not due to the stimulation by alloantigens, since the restoration of antigen-specific T cell proliferation by allo-M[phi], but not the allogeneic response, was abrogated by pretreatment of allo-M[phi] with poly I:C. These results are consistent with the hypothesis that poly I:C may modulate the expression of a cell surface costimulatory molecule on peritoneal M[phi] that is required for the activation and/or proliferation of resting T cells.
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Details
- Title
- Inhibition of macrophage-induced, antigen-specific T lymphocyte proliferation by poly I:C
- Creators
- Dawn A. Kirschmann
- Contributors
- Donna Murasko (Advisor) - Drexel University, Medical College of Pennsylvania (1970-1993)
- Awarding Institution
- Medical College of Pennsylvania
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Medical College of Pennsylvania; Philadelphia, Pennsylvania
- Number of pages
- xii, 204 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Medical College of Pennsylvania (1970-1993)
- Other Identifier
- 991021888829104721